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Nicotinic Receptors

Administration of nicotine in experimental animals has been reported to facilitate neurotransmitter release and synaptic transmission in thalamo-cortical, ascending mesolimbic-dopaminergic, noradrenergic, and cholinergic pathways.3233 To what extent any of these effects contributes to nicotine's cognitive-enhancing action is not known. However, the concentrations of nicotine required to elicit receptor up-regulation34-36 or increased neurotransmitter release32,37 require M concentrations....

The principal computerized test found useful for determining nicotine effects on cognitive function in adults with ADHD is the Conners continuous performance test (CPT).5,6 To characterize possible effects on other aspects of neurobehavioral function, components of the Automated Neuropsychological Assessment Metrics (ANAM) battery have also been used simple reaction time, spatial mental rotation, and delayed matching to sample.3435 The Conners CPT has been validated as an assessment tool for...

Recently, a derivative of epibatidine, ABT-594 has been developed by Abbott Laboratories as a nicotinic analgesic and, as mentioned earlier, is currently in phase II clinical trials. ABT-594 shows similar affinity to epibatidine at the human a4p2 subtype (Ki of 37 and 42 pM for ABT-594 and epibatidine, respectively), but has 4000 times less activity at the neuromus-cular receptor.77 The systemic administration of ABT-594 produced broad-spectrum antinociceptive activity in preclinical assays of...

As more experience working with nicotine in primates developed, it was noted that, when animals were tested on the day following nicotine pretreatment (in the absence of further drug or vehicle treatment), significant enhancement of performance efficiency continued to be maintained.23 Performance levels returned to prenicotine levels on the following day (i.e., within 36 hours after injection). This protracted feature of nicotine's beneficial mnemonic actions was unexpected, particularly in...

Acute nicotine administration has been shown to improve memory in a variety of tasks. It facilitates retention of avoidance training 1067 and enhances Morris water maze performance in young and aged rats.61 Also, acute nicotine treatment has been shown to reverse delay match to sample (DMTS) performance caused by aging, and facilitates performance in aged rats exhibiting deficits in spatial working memory1649 or poor passive avoidance performance due to a choline-deficient diet.58 In a series...

Antipsychotic drugs ameliorate the psychopathology and course of schizophrenia. Recent research has begun to examine how antipsychotic drugs affect smoking among patients with schizophrenia, how they affect nicotine-responsive phenotypes, and how these effects relate to the drugs' effects on psychopathology and cognitive psychomotor performance. An initial caveat in designing and evaluating studies in this area is that smoking approximately doubles the metabolic clearance rate of many...

Nicotinic receptor agonists have been shown to exert sexually dimorphic actions in laboratory animals. These nicotinic effects are as broadly physiological as sensory gating phenomenon,63 tuberoinfundibular dopaminergic neuron activity,64 active avoidance learning,65 and analgesia.66 The same may be said for nicotine's action in Nicotine Optimal Doses Young Monkeys Zero Delays Short Delays Medium Delays I Long Delays

Tourette's disorder (TD) is a neuropsychiatry disorder with childhood onset that is characterized largely by the expression of sudden, rapid and brief, recurrent, non-rhythmic, stereotyped motor movements (motor tics) and sounds (vocal tics) that are experienced as irresistible, but can be suppressed for varying lengths of time.1 These motoric symptoms range from relatively mild to very severe over the course of a patient's lifetime.23 Most patients with TD also exhibit comorbid neuropsychiatry...

Perhaps the most compelling revelation to emerge from the collective preclinical studies on nicotinic receptor-mediated antinociception is the remarkable breadth of animal pain models in which nicotinic agonists exhibit efficacy (Table 5.1). Thus, at least ten, biochemically and pharmacologically distinct agents have shown anti-nociceptive as well as antihyperalgesic antiallodynic activity in tests of mechanical, thermal, and chemical nociception. Interestingly, these agents are effective in...

Dopamine's role as a major central neurotransmitter, and its involvement in motor activity, were confirmed when it was found that one area of the brain in particular, the caudate nucleus, contained the highest concentration of DA of any tissue in the body (Bertler and Rosengren, 1959 Sano et al., 1959). This brain area was already known to mediate the extrapyramidal side effects of several drugs, and the experiments of Vander Eecken et al. (1960) and Adams et al. (1964) showed that patients...

Pharmacological characterization of nAChR can be assessed based on specific binding of radiolabeled nicotinic ligands and on competition by unlabeled compounds for specific radioligand binding. Central to this approach is identification of a suitable radioligand acting with reasonable selectivity binding with much lower affinity to other nAChR subtypes or specificity showing no binding to other nAChR subtypes at a given nAChR subtype s . Most radioligands for nAChR are agonists e.g., 3H-labeled...